2023-503640-14-00招募中3 期
Phase 3 Randomized, Controlled Study of Blinatumomab Alternating With Low-intensity Chemotherapy Versus Standard of Care for Older Adults With Newly Diagnosed Philadelphia-negative B-cell Precursor Acute Lymphoblastic Leukemia With Safety Run-in (Golden Gate Study)
Amgen Inc.91 个研究点 分布在 12 个国家目标入组 172 人开始时间: 2021年11月3日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 172
- 试验地点
- 91
- 主要终点
- SRI: Treatment-emergent adverse events, treatment-related adverse events, and adverse events of interest
研究概览
简要总结
Safety Run In (SRI): To evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy Phase 3 (Ph3): To compare event-free survival (EFS) of subjects receiving blinatumomab alternating with low-intensity chemotherapy to EFS of subjects receiving standard of care (SOC) chemotherapy Ph3: To compare overall survival (OS) of blinatumomab alternating with low-intensity chemotherapy to SOC chemotherapy
研究设计
- 分配方式
- Randomized
- 主要目的
- Phase 3 Part
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Subject has provided informed consent prior to initiation of any study specific activities/procedures OR Where permitted by local law, subject’s legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
- •Age ≥ 55 years at the time of informed consent OR Age 40 to < 55 years of age if at least 1 of the following comorbidities at the time of informed consent: - history of grades 3 and 4 pancreatitis - diabetes mellitus with end-organ damage - severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 10 x upper limit of normal (ULN) (liver cirrhosis must be confirmed by biopsy) - body mass index (BMI) ≥ 40 combined with relevant comorbidities such as metabolic syndrome - Any further combination of documented severe comorbidities that the investigator judges to be incompatible with administering an intensive pediatric-based, adult adapted standard chemotherapy regimen but still compatible with the suggested protocol for older subjects in both the experimental and the SOC arm. The subject history needs to be reviewed by the medical monitor during screening to determine enrollment acceptability based on a standard list with types of comorbidities allowed.
- •Subjects with newly diagnosed Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (ALL) per WHO criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, higher ECOG score allowed if due to underlying leukemia.
- •All subjects must have adequate organ function as defined below: - renal: estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 50 mL/min/1.73 m2 - liver function: total bilirubin ≤ 2x upper limit of normal (ULN; unless Gilbert’s Disease or if liver involvement with leukemia); exception for subjects 40 to < 55 years of age if comorbidity is per inclusion 102: severe liver disease such as cirrhosis stage 2 with portal hypertension or history of esophageal variceal bleeding and AST/ALT >10 x ULN (liver cirrhosis must be confirmed by biopsy) - cardiac: left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant, uncontrolled, or active cardiovascular disease (eg, myocardial infarction or stroke within 3 months). Consult with medical monitor as needed.
排除标准
- •Active CNS leukemia (i.e, CNS 3 leukemia, confirmed by lumbar puncture) not resolved with IT chemotherapy during screening
- •202 History of other malignancy within the past 3 years, with the following exceptions: - Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician. Note: History of other malignancy (eg, multiple myeloma) treated with immunomodulatory drugs (eg, lenalidomide, thalidomide) in the past 3 years is an exclusion. - Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. - Adequately treated cervical carcinoma in situ without evidence of disease. - Adequately treated breast ductal carcinoma in situ without evidence of disease. - Prostatic intraepithelial neoplasia without evidence of prostate cancer. - Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
- •History or presence of clinically relevant CNS pathology or eventsuch as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's diease, cerebellar disease, organic brain syndrome, or psychiatric conditions that preclude the use of high dose of corticosteroids. Consult with medical monitor as needed.
- •Current autoimmune disease or history of autoimmune disease with potential CNS involvement
- •Known infection with human immunodeficiency virus (HIV)
- •Known infection with chronic or active hepatitis B (eg, hepatitis b surface [HBs] antigen reactive or quantifiable hepatitis b virus [HBV] viral load) or hepatitis C virus (HCV) (eg, HCV RNA [qualitative] is detected). Active hepatitis B and C based on the following results: - Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B) - Negative HepBsAg and positive for hepatitis B core antibody: negative HBV DNA by PCR result is necessary to enroll. - Positive Hepatitis C virus antibody (HepCAb): negative hepatitis C virus RNA by PCR result is necessary to enroll.
- •Subject with symptoms and/or clinical signs and/or radiographic and/or sonographic signs that indicate an acute or uncontrolled chronic infection.
- •Cancer chemotherapy for this newly diagnosed B cell ALL before the start of protocol-required therapy with the exception of IT chemotherapy or pre-phase chemotherapy. Radiation to a spot lesion such as chloroma or lytic lesion of bone or vertebrae for pain or vertebral stabilization is allowed.
- •Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
研究组 & 干预措施
CYTARABINE
Test
干预措施: CYTARABINE (Drug)
DEXAMETHASONE, DEXAMETHASONE
Test
干预措施: DEXAMETHASONE (Drug)
ASPARAGINASE
Comparator
干预措施: ASPARAGINASE (Drug)
METHOTREXATE SODIUM, METHOTREXATE SODIUM
Comparator
干预措施: METHOTREXATE SODIUM (Drug)
PREDNISONE
Comparator
干预措施: PREDNISONE (Drug)
RITUXIMAB
Comparator
干预措施: RITUXIMAB (Drug)
PEGASPARGASE
Comparator
干预措施: PEGASPARGASE (Drug)
PREDNISOLONE
Comparator
干预措施: PREDNISOLONE (Drug)
IDARUBICIN
Comparator
干预措施: IDARUBICIN (Drug)
CRISANTASPASE
Comparator
干预措施: CRISANTASPASE (Drug)
CYCLOPHOSPHAMIDE
Test
干预措施: CYCLOPHOSPHAMIDE (Drug)
BLINATUMOMAB
Comparator
干预措施: BLINATUMOMAB (Drug)
VINCRISTINE SULFATE
Comparator
干预措施: VINCRISTINE SULFATE (Drug)
DOXORUBICIN
Comparator
干预措施: DOXORUBICIN (Drug)
MERCAPTOPURINE
Comparator
干预措施: MERCAPTOPURINE (Drug)
结局指标
主要结局
SRI: Treatment-emergent adverse events, treatment-related adverse events, and adverse events of interest
SRI: Treatment-emergent adverse events, treatment-related adverse events, and adverse events of interest
Ph3: EFS: time from randomization until treatment failure, relapse, or death from any cause, whichever is earlier. Subjects without an event will be censored at their last evaluable disease assessment date.
Ph3: EFS: time from randomization until treatment failure, relapse, or death from any cause, whichever is earlier. Subjects without an event will be censored at their last evaluable disease assessment date.
Ph3: OS: time from randomization until death due to any cause. Subjects alive will be censored at the date last known to be alive.
Ph3: OS: time from randomization until death due to any cause. Subjects alive will be censored at the date last known to be alive.
次要结局
- SRI: Complete remission (CR) by the end of the initial disease assessment period
- SRI: Minimal residual disease (MRD) response < 10-4 by the end of the initial disease assessment period
- Ph3: Change from baseline to end of the initial disease assessment period in global health status measured by the QLQ-C30 global health status quality of life scale
- SRI: Relapse-free survival (RFS): in subjects who achieve CR, the time from first achievement of this response until date of the first relapse including hematologic relapse, extramedullary relapse, or death due to any cause, whichever occurs first. Subjects without an event will be censored at their last evaluable disease assessment date.
- SRI: MRD RFS in subjects who achieve CR with MRD response, the time from first achievement of this response until date of the first relapse including molecular relapse, hematologic relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. Molecular relapse will be defined 2 ways: MRD ≥ 10-3 and MRD 10-4. Subjects without an event will be censored at their last evaluable disease assessment date.
- SRI: PK parameters for blinatumomab including, but not limited to, steady state concentration (Css) and clearance (CL)
- Ph3: Change from baseline to end of the initial disease assessment period in fatigue score measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue – Short Form 7a
- Ph3: Change from baseline to end of the initial disease assessment period in pain score measured by Brief Pain Inventory – Short Form (BPI-SF); Item 3: pain at its worst in the last 24 hours
- Ph3: Change from baseline to end of the initial disease assessment period in physical function measured by the QLQ-C30 functional scale
- Ph3: Change from baseline to end of the initial disease assessment period in nausea/vomiting measured by the QLQ-C30 symptom scale
- Ph3: CR by the end of the initial disease assessment period
- Ph3: MRD response < 10-4 by the end of the initial disease assessment period
- Ph3: RFS: in subjects who achieve CR, the time from first achievement of this response until date of the first relapse including hematologic relapse, extramedullary relapse, or death due to any cause, whichever occurs first. Subjects without an event will be censored at their last evaluable disease assessment date.
- Ph3: Relapse after autologous and allogeneic HSCT
- Ph3: MRD RFS in subjects who achieve CR with MRD response, the time from first achievement of this response until date of the first relapse including molecular relapse, hematologic relapse, and/or extramedullary relapse, or death due to any cause, whichever occurs first. Molecular relapse will be defined 2 ways: MRD ≥ 10-3 and MRD 10-4. Subjects without an event will be censored at their last evaluable disease assessment date.
- Ph3: MRD level over time
- Ph3: treatment-emergent adverse events, treatment related adverse events, and adverse events of interest
- Ph3: CD19 positive relapse and CD19 negative relapse identified by flow cytometry or immunocytochemistry for bone marrow (mandatory)
- Ph3: CD19 positive relapse and CD19 negative relapse identified by flow cytometry or immunohistochemistry for cerebrospinal fluid (mandatory)
- Ph3: CD19 positive relapse and CD19 negative relapse for extramedullary sites other than cerebrospinal fluid (optional - if data is available)
- Ph3: Lineage switch to acute myeloid leukemia (AML)
- Ph3: Localization of relapse by clinical assessment
- Ph3: Mortality in CR
- Ph3: Autologous and allogeneic HSCT in continuous first CR*
- Ph3: Mortality in CR after autologous and allogeneic HSCT*
- Ph3: Time to deterioration and time to improvements for fatigue score measured by PROMIS Fatigue – Short Form 7a
- Ph3: Time to deterioration and time to improvements for pain score measured by BPI-SF; Item 3: pain at its worst in the last 24 hours
- Ph3: Change from baseline in all other subscales of QLQ-C30 (role, cognitive, emotional, and social scales; pain and fatigue scales; single items: dyspnea, loss of appetite, insomnia, constipation, diarrhea, and perceived financial impact)
- Ph3: Time to deterioration and time to improvements for global health status, physical function, and nausea/vomiting scales.
- Ph3: Css and CL
研究者
Medical Information
Scientific
Amgen Inc.
研究点 (91)
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